MDC Researchers Reconstruct Jumping Gene
They can be found in plants, animals and even in humans – inactive remains of jumping genes, transposons. Researchers are striving to develop active transposons from these remains, using them as tools to decode gene function. At the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, researchers have now succeeded in reconstructing the first active transposon of the Harbinger transposon superfamily. In the laboratory, the artificial transposon developed by Dr. Ludivine Sinzelle, Dr. Zsuzsanna Izsvák, and Dr. Zoltán Ivics also shows cut-and-paste transposition in human cells and promises to serve as a useful experimental system for investigating human gene function. The findings of the MDC researchers have just been published online in the Proceedings of the National Academy of Sciences (PNAS)*.
Transposons
comprise about half of the human genome. “They are molecular parasites, similar
to fleas, only that they are in the genome of the host and not on its back,”
Dr. Zoltán Ivics explained. They jump, move, and proliferate through the host,
without whom they could not survive. In most cases, transposons do not fulfill
any function in the human genome. “However, not all are superfluous,” Dr. Ivics
went on to say. “More than 100 active genes, including some associated with the
immune system, have been
recognized as probably derived from transposons.”
To reconstruct
an active transposon, Dr. Ivics’ team compared the DNA of various inactive Harbinger transposons, one of the
largest superfamilies of transposons. Based on these results, they developed an
artificial jumping gene. “We were very lucky,” Dr. Ivics said. “The very first
experiment was successful.”
New tool for basic research
In the
cell lab, the MDC researchers inserted the transposon into the human cell by
means of a gene shuttle. Via a cut-and-paste mechanism, the artificial
transposon excises itself from its transport vehicle and inserts itself into
the genome of the cell. If the transposon jumps into an important gene and
deactivates it, it may impair important processes in the cell. As a result,
researchers can draw conclusions about the function of the gene.
Moreover,
in the course of evolution, transposons have been responsible for the emergence
of new genes. Thus, through computerized gene analysis, Dr. Ivics’ research
team has discovered two new elements related to the normal'>Harbinger transposon. In a new project, Dr. Ivics aims to elucidate
just what role these play in the human body.
Over the
long term, scientists hope to use such transposons in gene therapy as well.
With the aid of a transposon, an intact copy of a gene could be incorporated into
the genome of a patient to repair a defective gene. “But until this can happen,
there is still a lot to be done,” Dr. Ivics pointed out. “The new gene should
not just jump in anywhere.”
*Transposition of a Reconstructed Harbinger
Element in Human Cells and Functional Homology with Two Transposon-derived
Cellular Genes
Ludivine Sinzelle1, Vladimir V. Kapitonov,2, Dawid
P. Grzela1, Tobias Jursch1, Jerzy Jurka2,
Zsuzsanna Izsvák1,3 and Zoltán Ivics1
1Max DelbrückCenter for Molecular Medicine, Berlin, Germany;
2Genetic Information Research Institute, Mountain View, California,
USA
3Institute of Biochemistry, Biological
ResearchCenter
of the Hungarian Academy of Sciences, Szeged, Hungary
Dr. Ludivine Sinzelle (second from left), Dr. Zoltán Ivics (fourth from left), Dr. Zsuzsanna Izsvák (fifth from left)
